Metallic implants are used in large numbers in the practice of orthopaedic surgery. All metals in use have finite corrosion rates. Associated with release of metal by corrosion or other reactions, there have been proposed a variety of clinical problems involving metabolic, immunologic, bacteriologic and carcinogenic responses. Research to elucidate the possible connections has been hampered by a lack of knowledge of the molecular form that the corrosion products take and the concentrations in which they are present in patients. In particular, it has been proposed that a variety of biologically active organometallic intermediate compounds exist as a result of corrosion in vivo. The object of this proposed research project is to detect, isolate, quantitate and partially identify the blood bourne organometallic compounds that arise from the corrosion of the two most common orthopaedic metallic alloy systems: stainless steel and cobalt-chromium. The studies proposed involve HPLC fractionation of serum and treated tissue fragments followed by atomic absorption spectroscopy. The studies have two important elements: 1. The use of a small animal/microsphere implant model to examine the effects of implant area/animal body weight ratio on the production of organometallic complexes and to predict the possible findings in patients. 2. The use of several longitudinal studies in patient populations to determine changes in blood metallic and organometallic content levels as sequelae to various orthopaedic implant procedures.